Novel mutations in HSF4 cause congenital cataracts in Chinese families.
Novel mutations in HSF4 cause congenital cataracts in Chinese families.
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HSF4新突变导致中国家庭先天性白内障
DOI：
10.1186/s12881-018-0636-3
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发表时间：
2018-08-24
影响因子：
--
通讯作者：
Yang J
中科院分区：
文献类型：
--
作者：
Cao Z;Zhu Y;Liu L;Wu S;Liu B;Zhuang J;Tong Y;Chen X;Xie Y;Nie K;Lu C;Ma X;Yang J
背景：先天性白内障是一种在出生时或儿童早期就表现出来的白内障，是儿童致盲的主要原因。到目前为止，已知不同染色体上的30多个基因会导致这种疾病。本研究的目的是确定中国先天性白内障家系的HSF 4突变，方法：从中国东南部招募了42个无关的非综合征型先天性白内障家系和112个种族匹配的对照。我们采用桑格测序方法来发现变异。为了证实新的突变，STR单倍型构建，以检查与先天性白内障的共分离。使用生物信息学工具，包括SIFT，Polyphen 2和Human Splicing tumor，评估了新突变的致病潜力。结果：在所有先天性白内障家系中均未发现HSF 4基因突变。在5个无血缘关系的先天性白内障家系中发现了5个新的HSF 4突变，分别为c.187 T > C（p.Phe63Leu）、c.218G > T（p.Arg73Leu）、c.233A > G（p.Tyr78Cys）、IVS 5 c.233-1G > A和c.314G > C（p.Ser105Thr）。这些突变与每个家族中所有受影响的个体共分离，在未受影响的家族成员或112个无关对照中未观察到。根据ACMG指南和使用InterVar软件，所有五种突变都被归类为疾病“致病性”。HSF 4基因突变与11.90%的中国先天性白内障家系有关。结论：在本研究中，我们发现了5个中国先天性白内障家系中的HSF 4基因新突变。我们的研究结果扩大了导致先天性白内障的HSF 4突变的谱，这可能有助于精准医学时代先天性白内障的分子诊断。
Background:Congenital cataract, a kind of cataract presenting at birth or during early childhood, is a leading cause of childhood blindness. To date, more than 30 genes on different chromosomes are known to cause this disorder. This study aimed to identify the HSF4 mutations in a cohort from Chinese families affected with congenital cataracts.Methods:Forty-two unrelated non-syndromic congenital cataract families and 112 ethnically matched controls from southeast China were recruited from the southeast of China. We employed Sanger sequencing method to discover the variants. To confirm the novel mutations, STR haplotypes were constructed to check the co-segregation with congenital cataract. The pathogenic potential of the novel mutations were assessed using bioinformatics tools including SIFT, Polyphen2, and Human Splicing Finder. The pathogenicity of all the mutations was evaluated by the guidelines of American College of Medical Genetics and InterVar software.Results:No previously reported HSF4 mutations were found in all the congenital cataract families. Five novel HSF4 mutations including c.187 T > C (p.Phe63Leu), c.218G > T (p.Arg73Leu), c.233A > G (p.Tyr78Cys), IVS5 c.233-1G > A and c.314G > C (p.Ser105Thr) were identified in five unrelated families with congenital cataracts, respectively. These mutations co-segregated with all affected individuals in each family were not observed in the unaffected family members or in 112 unrelated controls. All five mutations were categorized to be the disease "pathogenic" according to ACMG guidelines and using InterVar software. Mutations in the HSF4 were responsible for 11.90% Chinese families with congenital cataracts in our cohort.Conclusions:In the study, we identified five novel HSF4 mutations in Chinese families with congenital cataracts. Our results expand the spectrum of HSF4 mutations causing congenital cataracts, which may be helpful for the molecular diagnosis of congenital cataracts in the era of precision medicine.
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影响因子：
14.9
作者：
Desmet FO;Hamroun D;Lalande M;Collod-Béroud G;Claustres M;Béroud C
通讯作者：
Béroud C
影响因子：
3.1
作者：
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通讯作者：
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影响因子：
4.2
作者：
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Liu, Mugen
影响因子：
1
作者：
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通讯作者：
Waiswo, Mauro
影响因子：
9.8
作者：
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通讯作者：
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